This application is generally related to treatment of the heart, and more particularly to managing and preventing detrimental cardiac remodeling following myocardial infarction. Remodeling of the heart is a harmful physical change in the heart that occurs with heart failure, heart attack, and heart disease. Remodeling is characterized by enlargement of the heart and thinning of the heart walls. For example, after a heart attack, while the normal heart muscle responds normally to excitatory pulses, tissue that is damaged by the heart attack does not respond or responds in a slower than normal rate to excitatory pulses. The healthy tissue however, continuing to function normally, places increased stress on the damaged and marginalized tissue, thereby “stretching” it. The stretching increases the volume of blood held by the heart resulting in a short term increased blood output via a Frank-Sterling mechanism. In this way, the heart muscle behaves something like a rubber band—the more it is stretched, the more “snap” the heart generates. However, if cardiac muscle is overstretched, or if the heart is stretched repetitively over a long period of time, it eventually loses its “snap” and becomes flaccid (a form of remodeling). Remodeling progresses in stages. Following a heart attack or as a consequence of heart disease, the heart becomes rounder and larger. Heart muscle cells die and the heart as a pump gets weaker. If the remodeling is allowed to progress, the heart's main pumping chamber—the left ventricle—enlarges and changes shape, getting rounder. The heart also undergoes changes at the cell level.
The heart is divided into the right side and the left side. The right side, comprising the right atrium and ventricle, collects and pumps de-oxygenated blood to the lungs to pick up oxygen. The left side, comprising the left atrium and ventricle, collects and pumps oxygenated blood to the body. Oxygen-poor blood returning from the body enters the right atrium through the vena cava. The right atrium contracts, pushing blood through the tricuspid valve and into the right ventricle. The right ventricle contracts to pump blood through the pulmonic valve and into the pulmonary artery, which connects to the lungs. The blood picks up oxygen in the lungs and then travels back to the heart through the pulmonary veins. The pulmonary veins empty into the left atrium, which contracts to push oxygenated blood into the left ventricle. The left ventricle contracts, pushing the blood through the aortic valve and into the aorta, which connects to the rest of the body. Coronary arteries extending from the aorta provide the heart blood.
The heart's own pacemaker is located in the atrium and is responsible for initiation of the heartbeat. The heartbeat begins with activation of atrial tissue in the pacemaker region (i.e., the sinoatrial or “SA” node), followed by cell-to-cell spread of excitation throughout the atrium. The only normal link of excitable tissue connecting the atria to the ventricles is the atrioventricular (AV) node located at the boundary between the atria and the ventricles. Propagation takes place at a slow velocity, but at the ventricular end the bundle of His (i.e., the electrical conduction pathway located in the ventricular septum) and the bundle braides carry the excitation to many sites in the right and left ventricle at a relatively high velocity of 1-2 m/s. The slow conduction in the AV junction results in a delay of around 0.1 seconds between atrial and ventricular excitation. This timing facilitates terminal filling of the ventricles from atrial contraction prior to ventricular contraction. After the slowing of the AV node, the bundle of His separates into two bundle branches (left and right) propagating along each side of the septum. The bundles ramify into Purkinje fibers that diverge to the inner sides of the ventricular walls. This insures the propagation of excitatory pulses within the ventricular conduction system proceeds at a relative high speed when compared to the propagation through the AV node.
The syndrome of “heart failure” is a common course for the progression of many forms of heart disease. Heart failure may be considered to be the condition in which an abnormality of cardiac function is responsible for the inability of the heart to pump blood at a rate commensurate with the requirements of the metabolizing tissues, or can do so only at an abnormally elevated filling pressure. Typically, the elevated filling pressures result in dilatation of the left ventricular chamber. Etiologies that can lead to this form of failure include idiopathic cardiomyopathy, viral cardiomyopathy, and ischemic cardiomyopathy.
Heart failure is a chronic condition that affects over five million Americans, and is the most common reason for hospitalization among elderly persons. Contrary to its name, heart failure is not a heart attack. Neither does the heart suddenly stop beating. Heart failure means that the heart is failing to pump enough blood to meet the body's needs. It often occurs in patients whose hearts have been weakened or damaged by a heart attack or other conditions. As the heart continues to fail, patients may experience breathlessness, fluid build-up in the limbs and severe fatigue. Delays in response of the septum to excitatory pulse may cause contractions that are not simultaneous and therefore the ventricular contraction pattern is non-concentric. In this mode, the heart is beating inefficiently.
When the heart is working properly, both of its lower chambers (ventricles) pump at the same time and in sync with the pumping of the two upper chambers (atria). Up to 40 percent of heart failure patients, however, have disturbances in the conduction of electrical impulses to the ventricles (e.g., bundle branch block or intraventricular conduction delay). As a result, the left and right ventricles are activated at different times. When this happens, the walls of the left ventricle (the chamber responsible for pumping blood throughout the body) do not contract simultaneously, reducing the heart's efficiency as a pump. The heart typically responds by beating faster and dilating. This results in a vicious cycle of further dilation, constriction of the vessels in the body, salt and water retention, and further worsening of heart failure. These conduction delays do not respond to antiarrhythmics or other drugs.
Patients who have heart failure may be candidates to receive a pacemaker. A biventricular pacemaker is a type of implantable pacemaker designed to treat heart failure. A biventricular pacemaker can help synchronize the lower chambers by sending electrical signals simultaneously to the left ventricle and to the right ventricle. By stimulating both ventricles (biventricular pacing), the pacemaker makes the walls of the right and left ventricles pump together again. The heart is thus resynchronized, pumping more efficiently while causing less wear and tear on the heart muscle itself. This is why biventricular pacing is also referred to as cardiac resynchronization therapy (CRT).
For patients who suffer from heart failure, remodeling of the heart may occur. Remodeling associated with heart failure is characterized by enlargement of the heart's left ventricle. In addition, the left ventricle walls become thinner. There is an increased use of oxygen, greater degree of mitral valve regurgitation, and decreased ejection fraction. Remodeling sets off a “domino effect” of further damage to heart cells and more severe heart disease. Biventricular pacing of the present invention can potentially reverse the process. This beneficial effect on the heart is called “reverse remodeling.” Typical biventricular pacemakers use cathodal pulses of 2.5 volts in the atrium and 5 volts in the ventricle.